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Record W1976011051 · doi:10.1073/pnas.0905965106

Msh2-dependent DNA repair mitigates a unique susceptibility of B cell progenitors to <i>c-Myc</i> -induced lymphomas

2009· article· en· W1976011051 on OpenAlexafffund
Rajeev M. Nepal, Tong Li, Blerta Kolaj, Winfried Edelmann, Alberto Martín

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsUniversity of Toronto
FundersNational Cancer InstituteNational Institutes of HealthCanada Research ChairsLeukemia Research Foundation
KeywordsMSH2DNAProgenitor cellBiologyDNA repairCancer researchGeneticsMolecular biologyCell biologyComputational biologyChemistryDNA mismatch repairStem cell

Abstract

fetched live from OpenAlex

C-Myc is one of the most common targets of genetic alterations in human cancers. Although overexpression of c-Myc in the B cell compartment predisposes to lymphomas, secondary mutations are required for disease manifestation. In this article, we show that genetic deficiencies causing arrested B cell development and accumulation of B cell progenitors lead to accelerated lymphomagenesis in Emu c-myc transgenic mice. This result suggests that B cell progenitors are more prone than their mature counterparts to developing secondary oncogenic lesions that complement c-Myc in promoting transformation. To investigate the nature of these oncogenic lesions, we examined Emu c-myc mice deficient in mismatch repair function. We report that Msh2(-/-) Emu c-myc and Msh2(G674A/G674A) Emu c-myc mice rapidly succumb to pro-B cell stage lymphomas, indicating that Msh2-dependent mismatch repair function actively suppresses c-Myc-associated oncogenesis during early B cell development.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.278
Teacher spread0.259 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations14
Published2009
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicDNA Repair MechanismsFrench-language works237,207